Purpose: Cancer treatment with the anthracycline doxorubicin is accompanied by severe cardiotoxicity. However, any causal treatment is prevented by the underlying mechanisms not being fully understood so far. We focused on the endoplasmic reticulum (ER) stress sensor Glucose-related Protein 78 (GRP78) which binds unfolded proteins and represses adverse ER stress as it was previously discovered to be associated with evasion of tumor cells from anthracycline treatment. Additionally, membrane bound GRP78 was recently found to be a mediator for pro-and anti-apoptotic pathways. With the investigation of the role of GRP78 in doxorubicin cardiomyopathy we hope to derive a potential therapeutic approach. Methods: Isolated neonatal rat ventricular cardiac myocytes were treated with 0,5 or 1μM doxorubicin. In vitro GRP78 knockdown was established by 5nM siRNA while GRP78 overexpression was achieved by transfection with a recombinant
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